title: Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis.
abstract: BACKGROUND
  Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.
  
  
  METHODS
  We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).
  
  
  RESULTS
  We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).
  
  
  CONCLUSIONS
  The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
authors.forename: Ayman
authors.initials: A
authors.lastname: Chit
authors.forename: Charlene
authors.initials: C
authors.lastname: Soobiah
authors.forename: David
authors.initials: D
authors.lastname: Hallett
authors.forename: Genevieve
authors.initials: G
authors.lastname: Meier
authors.forename: Maggie H
authors.initials: MH
authors.lastname: Chen
authors.forename: Mariam
authors.initials: M
authors.lastname: Tashkandi
authors.forename: Chris T
authors.initials: CT
authors.lastname: Bauch
authors.forename: Mark
authors.initials: M
authors.lastname: Loeb
mesh_terms: D056738:Cross Protection / Q000235:genetics; D006801:Humans; D007252:Influenza Vaccines / Q000235:genetics* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000235:genetics* / Q000517:prevention & control* / Q000821:virology; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013045:Species Specificity; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000235:genetics / Q000627:therapeutic use
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated